Suppression of postsurgical recurrence of hepatocellular carcinoma treated with autologous formalin-fixed tumor vaccine, with special reference to glypican-3.

Autologous formalin-fixed tumor vaccine (AFTV) suppressed re-recurrence for more than 32 months of multiple-recurrent hepatocellular carcinoma based on hepatitis C virus-induced liver cirrhosis in a case with previous recurrence interval, 51-, 28-, 12-, and 4-months. We detected glypican-3-specific cytotoxic T lymphocytes in the peripheral blood at 12 months after AFTV.

Clinical activity after 12 weeks of treatment with nonbiologics in early rheumatoid arthritis may predict articular destruction 2 years later.

OBJECTIVE: To investigate earlier prediction of future articular destruction in patients with early rheumatoid arthritis (RA). METHODS: We randomly allocated patients with RA with disease duration < 2 years to different nonbiologic disease modifying antirheumatic drug (DMARD) therapies in a double-blind trial. Progression of articular destruction over the 96-week treatment period was assessed using the modified Sharp method. RESULTS: Progression of articular destruction correlated more strongly with the American College of Rheumatology (ACR) core set measures after 12 weeks of treatment than with pretreatment values. Multiple regression analysis of data after 12 weeks yielded a correlation coefficient of 0.711. The sensitivity and specificity to predict articular destruction over the 75th percentile of the cohort were 78.6% and 84.6%, respectively. Patients who showed articular destruction over the 75th percentile of the cohort had low response to treatment at 12 weeks, and continued to have high clinical disease activity thereafter. Contrasting data were found in patients with slow progression of articular destruction. CONCLUSION: In patients with early RA, ACR core set measures after 12 weeks of nonbiologic DMARD treatment may predict articular destruction 2 years later. Low response to treatment at 12 weeks and continuing high disease activity thereafter were found in patients with rapid radiological progression. These data can be used to determine the appropriateness of treatment at 12 weeks and aid the decision to introduce biologic DMARD.

Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter, double-blind, randomized controlled study.

Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group), 200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 +/- 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 +/- 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.

[A case of probable bacterial translocation-associated sepsis in healthy adult].

We report a patient with bacterial translocation-associated sepsis who was healthy and did not have any related-background. The 57-year-old male had been well until 16 hours before admission, when nausea and vomiting gradually developed and increased in intensity. In the morning of May 22, 2002, he had shaking chills, temperature of 38.6 degrees C and watery diarrhea, and was admitted to Kawasaki Municipal Hospital. On admission, temperature was 40.7 degrees C but otherwise physical examination revealed no particular abnormality. Laboratory data showed total white blood cells of 28,400/microliter, platelet count of 130,000/microliter, creatinine of 2.0 mg/dl and C-reactive protein of 7.5 mg/dl. 1 g of cefmetazole was administered every eight hours. In the early morning of May 23, he suddenly went into shock. At that time, laboratory findings revealed total white blood cells of 33,700/microliter, platelet count of 65,000/microliter, C-reactive protein of 24.9 mg/dl, creatinine of 5.6 mg/dl and serum potassium concentration of 5.7 mEq/l. Gram positive cocci and gram negative rods were isolated from blood culture obtained on admission. Cefmetazole was changed to 1.5 g/day of imipenem/cilastatin sodium and 600 mg/day of clindamycin. In addition, hemodialysis and endotoxin removal with an adsorbent column using polymyxin B were performed. Bacteria detected in the blood on admission were identified as Klebsiela oxytoca and Enterococcus faecium. Imipenem/cilastatin sodium and clindamycin were continued for 13 days. The patient recovered fully and was discharged on June 11. This case suggests that bacterial translocation-associated sepsis might occur even in a hitherto healthy adult.

Anti-c-Mpl (thrombopoietin receptor) autoantibody-induced amegakaryocytic thrombocytopenia in a patient with systemic sclerosis.

Amegakaryocytic thrombocytopenia (AMT) associated with systemic sclerosis (SSc) has been described in several case reports, but the underlying mechanisms have not been identified. Here we describe a rare case of SSc accompanied by thrombocytopenia and megakaryocytic hypoplasia, in which autoantibody against thrombopoietin receptor (c-Mpl) was detected. A 61-year-old woman with limited SSc was admitted to our hospital because of severe thrombocytopenia (platelet count 0.2 x 10(4)/mm(3)) with gingival bleeding. Her bone marrow was hypocellular with absent megakaryocytes, consistent with AMT. Treatment with corticosteroids and intravenous immunoglobulin infusions resulted in an increased platelet count, and she sustained a remission over a 1-year period, with a platelet count averaging 10.0 x 10(4)/mm(3). Her serum was strongly positive for anti-c-Mpl antibody, and IgG fraction purified from her serum inhibited thrombopoietin-dependent cell proliferation in vitro. Our case report suggests that AMT in patients with SSc could be mediated by the anti-c-Mpl antibody, which functionally blocks an interaction between thrombopoietin and c-Mpl.